IN VIVO OPTICAL DIAGNOSIS OF ORAL MALIGNANCY IN HUMAN SUBJECTS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 目的：早期发现癌症及其可治愈的前兆仍然是确保患者生存和生活质量的最佳方法。尽管在治疗方面取得了重大进展，但口腔癌每年仍导致10，000名美国人死亡，主要是由于大多数口腔病变的晚期发现。具体目标：使用非侵入性光学体内技术的组合来测试人类受试者中口腔癌前病变和恶性肿瘤的非侵入性诊断的多模态方法。研究方法：在30例健康，发育不良，和/或恶性口腔组织，在体内光学相干断层扫描（OCT）和光学多普勒断层扫描（ODT）映射上皮，上皮下和血管的变化，在特定的，标记的网站之前，常规活检。离体多波长多光子（MPM）和二次谐波产生（SHG）荧光技术提供了关于表面和亚表面组织结构的平行数据，特别是胶原蛋白存在和结构、细胞存在和脉管系统。图像由2名设盲的、预先标准化的研究者使用0-6的标准化量表对所有模式进行诊断。制备组织学切片，并以0-6的评分进行病理学评价。ANOVA技术比较了成像诊断与组织病理学。使用ROC曲线和kappa统计量确定OCT/ODT+ MPM/SHG诊断能力的灵敏度和特异性的95%置信限。结果：获得的图像数据具有良好的准确性。在2 mm的组织深度，发育不良和恶性相关的结构和血管变化清晰可见。灵敏度（单独OCT/ODT：72-89%; OCT+MPM/SHG：76-90%）和特异性（单独OCT：68-84%;OCT+MPM/SHG：74-88%）与传统技术相比。结论：OCT/ODT和MPM/SHG是口腔发育不良和恶性肿瘤的有前途的非侵入性体内诊断方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objectives: Early detection of cancer and its curable precursors remains the best way to ensure patient survival and quality of life. Despite significant advances in treatment, oral cancer still results in 10,000 U.S. deaths annually, mainly due to the late detection of most oral lesions. Specific aim: Using a combination of non-invasive optical in vivo technologies to test a multi-modality approach to non-invasive diagnostics of oral premalignancy and malignancy in human subjects. Methods: In 30 patients with healthy, dysplastic, and/or malignant oral tissues, in vivo optical coherence tomography (OCT) and optical Doppler tomography (ODT) mapped epithelial, subepithelial and vascular change in specific, marked sites prior to routine biopsy. Ex vivo multi-wavelength multi-photon (MPM) and second harmonic generated (SHG) fluorescence techniques provided parallel data on surface and subsurface tissue structure, specifically collagen presence and structure, cellular presence, and vasculature. Images were diagnosed by 2 blinded, pre-standardized investigators using a standardized scale from 0-6 for all modalities. Histopathological sections were prepared and pathology evaluated on a scale of 0-6. ANOVA techniques compared imaging diagnostics with histopathology. 95% confidence limits of the sensitivity and specificity were established for the diagnostic capability of OCT/ODT+ MPM/SHG using ROC curves and kappa statistics. Results: Imaging data were reproducibly obtained with good accuracy. Dysplasia- and malignancy-related structural and vascular changes were clearly visible to tissue depths of 2mm. Sensitivity (OCT/ODT alone: 72-89%; OCT+MPM/SHG: 76-90%) and specificity (OCT alone: 68-84%;OCT+MPM/SHG: 74-88%) compared well with conventional techniques. Conclusions: OCT/ODT and MPM/SHG are promising non-invasive in vivo diagnostic modalities for oral dysplasia and malignancy.